外周血淋巴细胞亚群及肿瘤标志物变化对晚期非小细胞肺癌免疫治疗疗效的预测价值

Predictive Value of Lymphocyte Subsets Combined with Serum Tumor Markers in Immunotherapy for Advanced Non-small Cell Lung Cancer

目的旨在探讨外周血淋巴细胞亚群及肿瘤标志物变化对晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者免疫治疗疗效的预测价值及临床意义。方法收集2018年9月~2021年11月于徐州医科大学附属医院接受免疫治疗的110例晚期NSCLC患者的临床资料,根据疗效分为有效组(n=36)和无效组(n=74)。比较不同疗效组、治疗前后患者外周血T淋巴细胞亚群(CD4^(+)绝对计数、CD8^(+)绝对计数、CD4^(+)/CD8^(+))及癌胚抗原(carcino-embryonic antigen,CEA)、细胞角质蛋白19片段抗原21-1(CYFRA21-1)水平的变化。并绘制受试者工作特征曲线(receiver operator characteristic,ROC)计算曲线下面积(area under curve,AUC),分析上述指标对NSCLC免疫治疗疗效的预测价值。结果治疗6周,有效组患者CD4^(+)、CD4^(+)/CD8^(+)数值明显高于无效组(P<0.01);治疗12周,有效组患者CD4^(+)、CD4^(+)/CD8^(+)数值均明显高于无效组,CD8^(+)水平明显低于无效组(P<0.01)。治疗6、12周,有效组患者CEA、CYFRA21-1水平均明显低于无效组(P<0.01)。同时本研究通过分析显示,程序性死亡受体配体1(programmed cell death ligand 1,PD-L1)表达与否、一线/多线治疗、单药/联合方案对免疫治疗效果的影响不明显。ROC曲线结果显示,T淋巴细胞亚群、CEA及CYFRA21-1三者联合检测评估NSCLC免疫治疗疗效的AUC为0.933,明显高于三者单独判断(P<0.05)。结论免疫治疗可以调节NSCLC患者的免疫功能,显著降低血清肿瘤标志物水平,因此动态监测淋巴细胞亚群及肿瘤标志物水平对晚期非小细胞肺癌免疫治疗疗效有重要的预测价值。

Objective We aimed to investigate the predictive value and clinical significance of peripheral blood lymphocyte subsets and tumor markers on the efficacy of immunotherapy among patients with advanced non-small cell lung cancer(NSCLC).Methods The clinical data of 110 patients with advanced NSCLC who received immunotherapy in Affiliated Hospital of Xuzhou Medical University from September 2018 to November 2021 were collected,and they were divided into effective group(36 cases)and ineffective group(74 cases)according to efficacy.The levels of T lymphocyte subsets(CD4^(+),CD8^(+),CD4^(+)/CD8^(+)),carcinoembryonic antigen(CEA)and cytokeratin 19 fragment antigen 21-1(CYFRA21-1)in peripheral blood of patients between different therapeutic groups and between before and after treatment were compared.Receiver operating characteristic(ROC)curve was plotted and area under the curve(AUC)was calculated to analyze the predictive value of the above indicators for post-treatment efficacy of NSCLC.Results After 6 weeks of immunotherapy,the CD4^(+),CD4^(+)/CD8^(+)values in the effective group were significantly higher than those in the ineffective group(P<0.01).After 12 weeks of immunotherapy,the CD4^(+),CD4^(+)/CD8^(+)values in the effective group were significantly higher than those in the ineffective group,and the CD8^(+)level was significantly lower than those in the ineffective group(P<0.01).After 6 weeks and 12 weeks of immunotherapy,the CEA and CYFRA21-1 levels in the effective group were significantly lower than those in the ineffective group(P<0.01).In addition,the expression of programmed cell death ligand 1(PD-L1),first-line/multi-line treatment,and monotherapy/combination therapy had no obvious impact on the effect of immunotherapy.ROC curve results showed that the AUC of combined detection of T lymphocyte subsets,CEA and CYFRA21-1 in evaluating the efficacy of immunotherapy for NSCLC was 0.933,which was significantly higher than that of the three alone(P<0.05).Conclusion Immunotherapy can regulate the immune function of the NSCLC,and significantly reduce the level of tumor markers in serum.Therefore,dynamic monitoring of lymphocyte subsets and tumor markers has important predictive value for the efficacy of immunotherapy for advanced NSCLC.